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overall survival lapatinib breast cancer

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https://www.readbyqxmd.com/read/29698927/a-randomized-phase-ii-trial-of-trastuzumab-plus-capecitabine-versus-lapatinib-plus-capecitabine-in-patients-with-her2-positive-metastatic-breast-cancer-previously-treated-with-trastuzumab-and-taxanes-wjog6110b-eltop
#1
Toshimi Takano, Junji Tsurutani, Masato Takahashi, Takeharu Yamanaka, Kazuko Sakai, Yoshinori Ito, Junya Fukuoka, Hideharu Kimura, Hidetaka Kawabata, Kenji Tamura, Koji Matsumoto, Kenjiro Aogi, Kazuhiko Sato, Kazuto Nishio, Kazuhiko Nakagawa, Toshiaki Saeki
BACKGROUND: For human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with progression on trastuzumab-based therapy, continuing trastuzumab beyond progression and switching to lapatinib combined with chemotherapy are both valid options. We conducted an open-label, randomized phase II trial to compare the efficacy of these strategies. PATIENTS AND METHODS: Women with HER2-positive MBC previously treated with trastuzumab and taxanes were randomly assigned to receive trastuzumab plus capecitabine (HX) or lapatinib plus capecitabine (LX)...
April 23, 2018: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29543566/survival-analysis-after-neoadjuvant-chemotherapy-with-trastuzumab-or-lapatinib-in-patients-with-human-epidermal-growth-factor-receptor-2-positive-breast-cancer-in-the-geparquinto-g5-study-gbg-44
#2
Michael Untch, Gunter von Minckwitz, Bernd Gerber, Christian Schem, Mahdi Rezai, Peter A Fasching, Hans Tesch, Holm Eggemann, Claus Hanusch, Jens Huober, Christine Solbach, Christian Jackisch, Georg Kunz, Jens-Uwe Blohmer, Maik Hauschild, Tanja Fehm, Valentina Nekljudova, Sibylle Loibl
Purpose The GeparQuinto phase III trial demonstrated a lower pathologic complete response (pCR; pT0 ypN0) rate when lapatinib was added to standard anthracycline-taxane chemotherapy compared with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer. Here, we report the long-term outcomes. Methods Patients with HER2-positive tumors (n = 615) received neoadjuvant treatment with epirubicin (E) plus cyclophosphamide (C), followed by docetaxel (T) in combination with either lapatinib (L) or trastuzumab (H; ECH-TH arm: n = 307; ECL-TL arm: n = 308)...
March 15, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29413684/human-epidermal-receptor-family-inhibitors-in-patients-with-erbb3-mutated-cancers-entering-the-back-door
#3
Loic Verlingue, Antoine Hollebecque, Ludovic Lacroix, Sophie Postel-Vinay, Andrea Varga, Yolla El Dakdouki, Capucine Baldini, Rastilav Balheda, Anas Gazzah, Jean-Marie Michot, Aurélien Marabelle, Olivier Mir, Monica Arnedos, Etienne Rouleau, Eric Solary, Thierry De Baere, Eric Angevin, Jean-Pierre Armand, Stefan Michiels, Fabrice André, Eric Deutsch, Jean-Yves Scoazec, Jean-Charles Soria, Christophe Massard
INTRODUCTION: Therapeutic inhibition of the human epidermal receptor 3 (ERBB3, HER3) has been challenged by the low frequency of ERBB3 somatic alterations across cancer types. We have evaluated the clinical utility to use available inhibitors of the HER family in the context of ERBB3 mutations. PATIENTS AND METHODS: In this study, we have selected patients with somatic ERBB3 alterations detected in their tumours from the molecular screening programs running at our institution...
March 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29274446/progressively-enlarging-cerebellar-hematoma-concurrent-with-t-dm1-treatment
#4
Marcelo D Vilela, William T Longstreth, Hugo A S Pedrosa, Gabriel O B Gil, Juliano M Duarte, Marco Antonio D Filho
BACKGROUND: Trastuzumab emtansine, an antibody-drug conjugate commonly abbreviated as T-DM1, is accepted as effective therapy for trastuzumab-resistant metastatic HER2-positive breast cancer. T-DM1 significantly increases progression-free and overall survival when compared with lapatinib plus capecitabine in patients with HER2-positive breast cancer previously treated with trastuzumab and a taxane. Among the common side effects related to T-DM1, thrombocytopenia and mucosal hemorrhage are seen, although they are infrequently judged to be clinically significant...
March 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29244528/phase-iii-randomized-study-of-dual-human-epidermal-growth-factor-receptor-2-her2-blockade-with-lapatinib-plus-trastuzumab-in-combination-with-an-aromatase-inhibitor-in-postmenopausal-women-with-her2-positive-hormone-receptor-positive-metastatic-breast-cancer
#5
Stephen R D Johnston, Roberto Hegg, Seock-Ah Im, In Hae Park, Olga Burdaeva, Galina Kurteva, Michael F Press, Sergei Tjulandin, Hiroji Iwata, Sergio D Simon, Sarah Kenny, Severine Sarp, Miguel A Izquierdo, Lisa S Williams, William J Gradishar
Purpose Human epidermal growth factor receptor 2 (HER2) targeting plus endocrine therapy (ET) improved clinical benefit in HER2-positive, hormone receptor (HR)-positive metastatic breast cancer (MBC) versus ET alone. Dual HER2 blockade enhances clinical benefit versus single HER2 blockade. The ALTERNATIVE study evaluated the efficacy and safety of dual HER2 blockade plus aromatase inhibitor (AI) in postmenopausal women with HER2-positive/HR-positive MBC who received prior ET and prior neo(adjuvant)/first-line trastuzumab (TRAS) plus chemotherapy...
March 10, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29231164/lapatinib-plus-capecitabine-in-patients-with-her2-positive-metastatic-breast-cancer-a-systematic-review
#6
REVIEW
Rebecca Madden, Sam Kosari, Gregory M Peterson, Nasser Bagheri, Jackson Thomas
OBJECTIVE: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which accounts for 20 - 25% of cases of breast cancers, is highly aggressive. Due to cardiotoxicity and increasing resistance associated with trastuzumab, the first-line treatment, there is a need for effective second-line therapies in treating HER2-positive breast cancer. In this context, there has been increasing interest in the combination of lapatinib plus capecitabine. The aim of this systematic review was to assess the efficacy of lapatinib plus capecitabine for HER2-positive breast cancer after progression with trastuzumab therapy, in comparison with capecitabine monotherapy and other agents such as vinorelbine and trastuzumab emtansine...
February 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29129754/cd44-targeting-hyaluronic-acid-coated-lapatinib-nanocrystals-foster-the-efficacy-against-triple-negative-breast-cancer
#7
Satish Agrawal, Monika Dwivedi, Hafsa Ahmad, Sangappa Basanna Chadchan, Abhishek Arya, Roshan Sikandar, Shweta Kaushik, Kalyan Mitra, Rajesh Kumar Jha, Anil Kumar Dwivedi
Lapatinib (LPT) is an orally administered drug for the treatment of metastatic breast cancer. For expanding its therapeutic horizon, we have prepared its nanocrystals (LPT-NCs) that were subsequently coated with hyaluronic acid (HA) to produce LPT-HA-NCs. The detailed in-vitro and in-vivo investigation of LPT-HA-NCs showed the superior anticancer activity due to active targeting to CD44 receptors than the counterparts LPT-NCs and free LPT. In the triple negative 4T1 cells induced breast tumor bearing female Balb/C mice; LPT-HA-NCs treatment caused significant retardation of tumor growth and overall increase in animal survival probability because of their higher tumor localization, increased residence time...
February 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29063053/management-of-breast-cancer-brain-metastases-focus-on-human-epidermal-growth-factor-receptor-2-positive-breast-cancer
#8
REVIEW
Peng Yuan, Song-Lin Gao
After the introduction of trastuzumab, a monoclonal antibody that binds to human epidermal growth factor receptor 2 (HER2), the overall survival (OS) among patients with HER2-positive breast cancer has been substantially improved. However, among these patients, the incidence of brain metastases (BM) has been increasing and an increased proportion of them have died of intracranial progression, which makes HER2-positive breast cancer brain metastases (BCBM) a critical issue of concern. For local control of limited BM, stereotactic radiosurgery (SRS) and surgical resection are available modalities with different clinical indications...
March 25, 2017: Chronic diseases and translational medicine
https://www.readbyqxmd.com/read/29022084/exposure-response-analyses-of-trastuzumab-emtansine-in-patients-with-her2-positive-advanced-breast-cancer-previously-treated-with-trastuzumab-and-a-taxane
#9
Chunze Li, Bei Wang, Shang-Chiung Chen, Russell Wada, Dan Lu, Xin Wang, Daniel Polhamus, Jonathan French, Shweta Vadhavkar, Alexander Strasak, Melanie Smitt, Amita Joshi, Meghna Samant, Angelica Quartino, Jin Jin, Sandhya Girish
PURPOSE: In the phase III EMILIA study, trastuzumab emtansine (T-DM1) significantly improved progression-free survival (PFS) and overall survival (OS) versus capecitabine plus lapatinib (control) in previously treated human epidermal growth factor receptor 2-positive advanced breast cancer. Using EMILIA data, we evaluated the T-DM1 exposure-response relationship. METHODS: Exposure-response relationships were examined with four exposure metrics [model-predicted and observed minimum concentration (Cmin ) and area under the concentration-time curve from time zero to day 21 of T-DM1 at cycle 1] and multiple efficacy (OS, PFS, objective response rate) and safety (grade ≥ 3 adverse events, grade ≥ 3 thrombocytopenia, grade ≥ 3 hepatotoxicity) endpoints...
December 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28969087/efficacy-and-safety-of-t-dm1-in-the-common-practice-of-her2-advanced-breast-cancer-setting-a-multicenter-study
#10
Alessandra Fabi, Michelino De Laurentiis, Michele Caruso, Enrichetta Valle, Luca Moscetti, Daniele Santini, Katia Cannita, Luisa Carbognin, Mariangela Ciccarese, Rosalba Rossello, Grazia Arpino, Vita Leonardi, Filippo Montemurro, Nicla La Verde, Daniele Generali, Alberto Zambelli, Giuseppa Scandurra, Michelangelo Russillo, Ida Paris, Anna Maria D'Ottavio, Gianfranco Filippelli, Marianna Giampaglia, Simonetta Stani, Agnese Fabbri, Daniele Alesini, Daniela Cianniello, Diana Giannarelli, Francesco Cognetti
Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28810186/the-efficacy-of-lapatinib-and-capecitabine-in-her-2-positive-breast-cancer-with-brain-metastases-a-systematic-review-and-pooled-analysis
#11
REVIEW
Fausto Petrelli, Michele Ghidini, Veronica Lonati, Gianluca Tomasello, Karen Borgonovo, Mara Ghilardi, Mary Cabiddu, Sandro Barni
INTRODUCTION: Breast cancer (BC) with HER-2/neu overexpression or amplification (HER-2+) is associated with a higher prevalence of brain metastases (BMs) when compared to other subtypes. Among approved drugs for HER-2+ BC, lapatinib (L) is associated with single agent activity toward BMs. We conducted a systematic review to determine the efficacy of L, singly or in combination with capecitabine (C), as a treatment for HER-2+ BMs. MATERIAL AND METHODS: We searched PubMed, EMBASE, The Cochrane Library, SCOPUS, Web of Science, ClinicalTrials...
October 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28750133/role-of-cytotoxic-tumor-infiltrating-lymphocytes-in-predicting-outcomes-in-metastatic-her2-positive-breast-cancer-a-secondary-analysis-of-a-randomized-clinical-trial
#12
COMPARATIVE STUDY
Shuzhen Liu, Bingshu Chen, Samantha Burugu, Samuel Leung, Dongxia Gao, Shakeel Virk, Zuzana Kos, Wendy R Parulekar, Lois Shepherd, Karen A Gelmon, Torsten O Nielsen
Importance: Accumulating evidence indicates that tumor-infiltrating lymphocytes (TILs) are associated with clinical outcomes and may predict the efficacy of chemotherapy and human epidermal growth factor receptor 2 (HER2, encoded by the gene ERBB2)-targeted therapy in patients with HER2-positive breast cancer. Objective: To investigate the role of TILs, particularly cytotoxic CD8+ T cells, in the prediction of outcomes in patients with HER2-positive metastatic breast cancer randomized to an antibody-based (trastuzumab) vs a small molecule-based (lapatinib) anti-HER2 therapy...
November 9, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28670138/sr-b1-targeted-nanodelivery-of-anti-cancer-agents-a-promising-new-approach-to-treat-triple-negative-breast-cancer
#13
Rebecca Johnson, Nirupama Sabnis, Xiangle Sun, Ruhani Ahluwalia, Andras G Lacko
Patients with triple-negative breast cancer (TNBC) have a considerably less favorable prognosis than those with hormone-positive breast cancers. TNBC patients do not respond to current endocrine treatment and have a 5-year survival prognosis of <30%. The research presented here is intended to fill a void toward the much needed development of improved treatment strategies for metastatic TNBC. The overall goal of this research was to evaluate the effectiveness of reconstituted high-density lipoprotein (rHDL) nanoparticles (NPs) as delivery agents for anti-TNBC drugs...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28526538/trastuzumab-emtansine-versus-treatment-of-physician-s-choice-in-patients-with-previously-treated-her2-positive-metastatic-breast-cancer-th3resa-final-overall-survival-results-from-a-randomised-open-label-phase-3-trial
#14
RANDOMIZED CONTROLLED TRIAL
Ian E Krop, Sung-Bae Kim, Antonio Gonzalez Martin, Patricia M LoRusso, Jean-Marc Ferrero, Tanja Badovinac-Crnjevic, Silke Hoersch, Melanie Smitt, Hans Wildiers
BACKGROUND: In the randomised, parallel assignment, open-label, phase 3 TH3RESA study, progression-free survival was significantly longer with trastuzumab emtansine versus treatment of physician's choice in previously treated patients with HER2-positive advanced breast cancer. We report results from the final overall survival analysis of the TH3RESA trial. METHODS: Eligible patients for the TH3RESA trial were men and women (aged ≥18 years) with centrally confirmed HER2-positive advanced breast cancer previously treated with both trastuzumab and lapatinib (advanced setting) and a taxane (any setting) and with progression on two or more HER2-directed regimens in the advanced setting...
June 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28526536/trastuzumab-emtansine-versus-capecitabine-plus-lapatinib-in-patients-with-previously-treated-her2-positive-advanced-breast-cancer-emilia-a-descriptive-analysis-of-final-overall-survival-results-from-a-randomised-open-label-phase-3-trial
#15
RANDOMIZED CONTROLLED TRIAL
Véronique Diéras, David Miles, Sunil Verma, Mark Pegram, Manfred Welslau, José Baselga, Ian E Krop, Kim Blackwell, Silke Hoersch, Jin Xu, Marjorie Green, Luca Gianni
BACKGROUND: The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. METHODS: EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane...
June 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28415567/efficacy-and-safety-of-t-dm1-in-the-common-practice-of-her2-advanced-breast-cancer-setting-a-multicenter-study
#16
Alessandra Fabi, Michelino De Laurentiis, Michele Caruso, Enrichetta Valle, Luca Moscetti, Daniele Santini, Katia Cannita, Luisa Carbognin, Mariangela Ciccarese, Rosalba Rossello, Grazia Arpino, Vita Leonardi, Filippo Montemurro, Nicla La Verde, Daniele Generali, Alberto Zambelli, Giuseppa Scandurra, Michelangelo Russillo, Ida Paris, Anna Maria D'Ottavio, Gianfranco Filippelli, Marianna Giampaglia, Simonetta Stani, Agnese Fabbri, Daniele Alesini, Daniela Cianniello, Diana Giannarelli, Francesco Cognetti
Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28376188/regional-nodal-irradiation-after-breast-conserving-surgery-for-early-her2-positive-breast-cancer-results-of-a-subanalysis-from-the-altto-trial
#17
RANDOMIZED CONTROLLED TRIAL
Isabelle Gingras, Eileen Holmes, Evandro De Azambuja, David H A Nguyen, Miguel Izquierdo, Jo Anne Zujewski, Moshe Inbar, Bjorn Naume, Gianluca Tomasello, Julie R Gralow, Antonio C Wolff, Lyndsay Harris, Michael Gnant, Alvaro Moreno-Aspitia, Martine J Piccart, Hatem A Azim
Background: Two randomized trials recently demonstrated that regional nodal irradiation (RNI) could reduce the risk of recurrence in early breast cancer; however, these trials were conducted in the pretrastuzumab era. Whether these results are applicable to human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with anti-HER2-targeted therapy is unknown. Methods: This retrospective analysis was performed on patients with node-positive breast cancer who were enrolled in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization phase III adjuvant trial and subjected to BCS...
August 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28375706/impact-of-diabetes-insulin-and-metformin-use-on-the-outcome-of-patients-with-human-epidermal-growth-factor-receptor-2-positive-primary-breast-cancer-analysis-from-the-altto-phase-iii-randomized-trial
#18
RANDOMIZED CONTROLLED TRIAL
Amir Sonnenblick, Dominique Agbor-Tarh, Ian Bradbury, Serena Di Cosimo, Hatem A Azim, Debora Fumagalli, Severine Sarp, Antonio C Wolff, Michael Andersson, Judith Kroep, Tanja Cufer, Sergio D Simon, Pamela Salman, Masakazu Toi, Lyndsay Harris, Julie Gralow, Maccon Keane, Alvaro Moreno-Aspitia, Martine Piccart-Gebhart, Evandro de Azambuja
Purpose Previous studies have suggested an association between metformin use and improved outcome in patients with diabetes and breast cancer. In the current study, we aimed to explore this association in human epidermal growth factor receptor 2 (HER2 ) -positive primary breast cancer in the context of a large, phase III adjuvant trial. Patients and Methods The ALTTO trial randomly assigned patients with HER2-positive breast cancer to receive 1 year of either trastuzumab alone, lapatinib alone, their sequence, or their combination...
May 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28349782/hr-her2-breast-cancers-with-growth-factor-receptor-mediated-emt-have-a-poor-prognosis-and-lapatinib-downregulates-emt-in-mcf-7-cells
#19
Krisha Desai, Radhika Aiyappa, Jyothi S Prabhu, Madhumathy G Nair, Patrick Varun Lawrence, Aruna Korlimarla, Anupama Ce, Annie Alexander, Rohini S Kaluve, Suraj Manjunath, Marjorrie Correa, B S Srinath, Shekhar Patil, Anjali Kalamdani, Msn Prasad, T S Sridhar
Despite an overall good prognosis, a significant proportion of patients with hormone receptor positive human epidermal growth factor receptor 2 negative breast cancers develop distant metastases. The metastatic potential of epithelial cells is known to be regulated by tumor-stromal interaction and mediated by epithelial-to-mesenchymal transition. Hormone receptor positive human epidermal growth factor receptor 2 negative tumors were used to estimate markers of epithelial-to-mesenchymal transition, and the luminal breast cancer cell line MCF-7 was used to examine the interactions between integrins and growth factor receptors in causation of epithelial-to-mesenchymal transition...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28289045/efficacy-and-safety-of-lapatinib-and-trastuzumab-for-her2-positive-breast-cancer-a-systematic-review-and-meta-analysis-of-randomised-controlled-trials
#20
REVIEW
Zhi-Qiao Xu, Yan Zhang, Ning Li, Pei-Jie Liu, Ling Gao, Xin Gao, Xiao-Jing Tie
OBJECTIVES: The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour actively in models of HER2-positive breast cancer. However, the efficacy of trastuzumab in combination with lapatinib remains controversial. Therefore, we conducted this meta-analysis to compare combination treatment with lapatinib and trastuzumab to trastuzumab or lapatinib alone in the treatment of HER2-positive breast cancer...
March 13, 2017: BMJ Open
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